Introduction: There is a paucity of large-scale data from multiethnic populations on proteomic alterations related to type 2 diabetes, which could help identify prognostic mediators.

Method: We analyzed 4,955 plasma proteins using SomaLogic v4.0 on 10,478 ARIC Study participants (Visit 2, 1990-92, mean age: 57±6 years, 56% women, 22% Black adults, 14% with diabetes) . We used logistic regression to quantify proteins associations with prevalent diabetes in a 2/3 discovery and 1/3 validation subset, with Bonferroni correction of P-values.

Results: After adjustment for demographics, clinical, and lifestyle risk factors (Figure) , 642 proteins were significantly associated with diabetes in the discovery sample (p<10−6) , with 3confirmed in the validation sample (p<0.05/642) . The top five findings were semaphorin-6A, plexin-B2, inactive tyrosine-protein kinase 7, cartilage intermediate layer protein 2, and semaphorin-6B. Proteins with known diabetes associations were also identified : insulin receptor, insulin-like growth factor-binding protein 2, growth differentiation factor-15, and adiponectin.

Conclusions: A large-scale proteomics approach identified numerous diabetes-related alterations. Pathway analysis and comparison to proteomic risk factors for diabetes incidence and complications will shed light on plasma proteomic consequences of diabetes and their relation to future risk.


J.B.Echouffo tcheugui: None. P.Lutsey: None. M.Grams: None. E.Selvin: Other Relationship; Wolters Kluwer. J.Coresh: Consultant; Ltd, Research Support; National Institutes of Health. J.Chen: None. M.R.Rooney: None. O.Tang: None. C.M.Ballantyne: Consultant; Abbott Diagnostics, Althera Pharmaceuticals, Amarin Corporation, Amgen Inc., Arrowhead Pharmaceuticals, Inc., AstraZeneca, Corvidia Therapeutics, Denka Seiken, ESPERION Therapeutics, Inc., Genentech, Inc., Gilead Sciences, Inc., Illumina, Matinas BioPharma Inc, Merck & Co., Inc., New Amsterdam, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Regeneron Pharmaceuticals Inc., Roche Diagnostics, Sanofi, Research Support; Abbott Diagnostics, Akcea Therapeutics, Amgen Inc., Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Ionis Pharmaceuticals, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals Inc., Roche Diagnostics. E.Boerwinkle: None. C.E.Ndumele: None. J.S.Pankow: None. R.Demmer: None.


National Institutes of Health (K23 HL153774)

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